Project Title: Alpha-synuclein aggregates are targeted for degradation by phase-separated proteasome droplets
Supervisor: Dr Yu Ye and Prof Steve Gentleman
Location: Sir Michael Uren Hub, White City Campus
I am a PhD student at the Dementia Research Institute (DRI) investigating the role of post-translational modifications of amyloid proteins in the pathogenesis of Alzheimer’s and Parkinson’s diseases. Prior to starting my PhD, I completed my BSc in Biochemistry at KCL, MRes at Imperial, and worked as a research technician in the Kinases and Brain Development laboratory at The Francis Crick Institute.
- 2018-2019 MRes Molecular and Cellular Biosciences, Imperial College London
- 2015-2018 BSc Biochemistry, King’s College London
Post-translational modifications on amyloid proteins have been shown to have critical roles involved in their aggregation behaviour. Enhanced phosphorylation and ubiquitination have been found in tau tangles in Alzheimer’s disease (AD) and Lewy Bodies in Parkinson’s disease (PD). In addition, both ubiquitinating and deubiquitinating enzymes, as well as ubiquitin-dependent degradation through the proteasome, have been implicated in AD and PD. Understanding the key enzymatic activities that drive toxic protein aggregation is therefore critical to identify novel targets of therapeutic intervention to slow and reverse neurodegeneration.
The aim of my PhD project is to study how alpha-synuclein aggregates are targeted by proteasomes for degradation and why aggregates are not cleared in neurodegenerative diseases. My project combines biochemistry and cell biology approaches with advanced super-resolution microscopy techniques.
Morten M., Sirvio L., Rupawala H., Mee Hayes E., Franco Budia A., Radulescu C., Rupawala H., Ying L., Barnes SJ., Muga A., Ye Y. “Quantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies.” Proceedings of the National Academy of Sciences, vol. 119, no. 41, 2022, https://doi.org/10.1073/pnas.2205591119
Mee Hayes E., Sirvio L., Ye Y. “A potential mechanism for targeting aggregates with proteasomes and disaggregases in liquid droplets.” Frontiers in Aging Neuroscience, vol. 14, 2022, https://doi.org/10.3389/fnagi.2022.854380
Presentations and conferences attended
"Aggregates are Targeted for Degradation by Phase-Separated Proteasome Droplets" at the Stress Proteins in Growth, Development and Disease Gordon Research Seminar (GRS) - July 1 - 2, 2023
Stress Proteins in Growth, Development and Disease Gordon Research Conference - July 2 - 7, 2023